Project Summary The availability of effective and generally well-tolerated antiretroviral therapy for people with HIV has translated into dramatically longer survival and life expectancy. While efforts at disease prevention and cure are needed and ongoing, an important focus is now on understanding the symptoms and co-morbidities of people living with HIV (PLWH). For example, fatigue and difficulty sleeping are very commonly reported by PLWH even while HIV is suppressed and with normal CD4 counts. Coronary artery disease, diabetes mellitus and neurocognitive decline are now recognized as important complications of HIV/ART. These symptoms and co-morbidities important in PLWH may also be symptoms and consequences of obstructive sleep apnea (OSA). OSA is defined by repetitive collapse of the upper airway during sleep, which leads to transient hypoxemia and arousals from sleep, and is associated with all of the cardiovascular, metabolic, and neurocognitive consequences listed above. OSA has been reported to occur in up to 70% of PLWH, but few are diagnosed and even fewer (<4% in some cohorts) are treated. OSA is increasingly recognized as a multifactorial disorder that can occur in different people for different reasons, not only due to anatomical predisposition (collapsibility of the upper airway), but also related to low arousal threshold (wake up too easily), dysfunction in upper airway dilator muscles and instability in ventilatory control. Through careful measurement of these underlying factors and the symptoms experienced by PLWH, this proposal seeks to understand how different mechanisms underlying OSA ? endotypes ? lead to different symptoms or consequences ? phenotypes ? in PLWH. For example, whether OSA contributes to fatigue in an individual with HIV, or whether that fatigue will improve with treatment of OSA, is not known. Our goals are: - To understand the contribution of OSA to symptoms important for PLWH, such as fatigue and cardiovascular disease - To compare the impact of different OSA endotypes on phenotypes on PLWH - To understand how underlying endotype mediates changes in phenotype seen with treatment of OSA